The field of the present invention is bone repair and replacement. More specifically, the invention relates to a self-hardening, osteogenic composition, which has desirable handling characteristics and mechanical properties.
Naturally-occurring bone is comprised of both organic and inorganic components. The organic component includes growth factors, cartilage, collagen, and other proteins. The inorganic bone component includes non-stoichiometric, poorly crystalline apatitic (PCA) calcium phosphate, having a Ca/P ratio between 1.45 and 1.75 (Besic et al. (1969) J. Dental Res. 48(1):131). This inorganic bone mineral is continuously resorbed and regenerated in vivo by osteoclasts and osteoblasts.
Bone implants are often used to augment the natural regeneration process in the event of bone defects and injuries. These implants must be biocompatible. Additionally, an ideal bone implant should be osteogenic, i.e., both osteoconductive and osteoinductive, easily manipulated by a surgeon prior to implantation, and of a strength and composition such that the implant will maintain its shape in vivo.
Given its regenerative capabilities, natural bone is a potential implant material. However, the use of autogenic, allogenic, and xenogeneic bone is complicated by associated disease transmission, immunogenic implant rejection, patient morbidity, and complicated surgical procedures. Thus, synthetic bone implant materials have become the focus of increasing attention.
Metal implant devices have been and continue to be used because of their high strength and stability. Despite these advantages, metal devices are disfavored because they cannot be resorbed into natural bone mineral and are, consequently, permanent foreign bodies once implanted.
To overcome the deficiencies of metal implants, compositions more closely approximating natural bone have been developed. Organic, osteoinductive materials are desirable components of such compositions. Commonly used osteoinductive materials include demineralized bone matrix (DBM) and recombinant human bone morphogenic proteins (rh-BMPs; see, e.g., U.S. Pat. No. 6,030,635; European Patent Appln. No. 0 419 275; PCT/US00/03024; PCT/US99/01677; and PCT/US98/04904). These organic, osteoinductive materials are typically delivered to in implant site in combination with a fluid or gelatinous carrier (see, e.g., U.S. Pat. Nos. 6,030,635; 5,290,558; 5,073,373; and PCT/US98/04904). An ideal bone implant includes substantial quantities of these osteoinductive materials so as to maximize its regenerative capabilities.
These organic, osteoinductive materials have previously been combined with hydroxyapatite and/or tricalcium phosphate to form synthetic bone compositions. The utility of these synthetic bone implants is offset by the tendency of the hydroxyapatite and/or tricalcium phosphate to inhibit the osteoinductivity of the organic component (see, e.g., Redondo, L. M. et al. (1995) Int. J. Oral Maxillofac. Surg. 24(6):445-448; Lindholm, T. C. et al. (1993) Ann. Chir. Gynaecol. Suppl. 207:91-98; Alper, G. et al. (1989) Am. J. Med. Sci. 298(6):371-376). More recently, organic, osteoinductive materials have been combined with resorbable calcium phosphate compositions, such as those including amorphous calcium phosphate and poorly crystalline apatitic (PCA) calcium phosphate (see, e.g., U.S. Pat. No. 6,027,742; PCT/US00/20630; and PCT/US00/03024). The mechanical strength of these implants, though, diminishes as larger quantities of the osteoinductive component (e.g., DBM) are incorporated. Furthermore, implants containing desirable amounts of osteoinductive materials tend to be difficult to manipulate and to lose their cohesiveness and shape in vivo. Therefore, there is a need for improved bone implant materials containing a calcium phosphate component and DBM particles that have a high compressive strength.